Support is requested to acquire a high-sensitivity 600 MHz triple resonance (1H, 13C, 15N) TCI cryoprobe and to upgrade an existing 600 MHz (1H Larmor frequency) NMR spectrometer console at Montana State University (MSU) to a more automated and high-throughput data collection platform (Bruker Avance IIITM). This instrumentation will be used by a diverse group of researchers from MSU Departments of Chemistry and Biochemistry, Veterinary Molecular Biology, Chemical and Biochemical Engineering, the Center for Biofilm Engineering, the Department of Cell Biology and Neuroscience, and the NIH Rocky Mountain Laboratory. Currently, none of the solution NMR spectrometers in the MSU Structural Biology and Chemistry NMR Facility are equipped with a cryoprobe, and the requested instrumentation and upgrade of the spectrometer console hardware will be the first of its kind on campus. The requested instrumentation upgrades will enhance sensitivity and maximize throughput of MSU 600 MHz solution NMR spectrometer. It will contribute significantly to the successful completion of challenging NMR-based structural biology projects and the expansion of NMR metabolomics research programs that are being developed on campus. The very substantially enhanced sensitivity achieved with the requested instrumentation will allow acquisition of experiments and studies on challenging biological samples, which are currently not possible because of limited sample solubility, limited sample stability, or limited instrument time availability. The console upgrade will allow automated shimming and performance optimization, and will provide much more efficient use of the recently purchased automatic sample loading system (Bruker SampleJetTM). The combination of the console upgrade and the automatic sample loading system will allow more effective 24/7 utilization of the 600 MHz NMR instrument. The cryoprobe and upgraded console will greatly facilitate the expansion of our existing NMR metabolomics capabilities (which include ChenomxTM and AMIXTM software for metabolite profiling analysis). Enhancement of NMR structural biology and metabolomics infrastructure is desired by a number of prospective users and supports the development of a new NIH-funded P20 Center for the Analysis of Cellular Mechanisms and Systems Biology. MSU's DRX 600 NMR instrument is used quite heavily, but the enhanced sensitivity and performance provided by the requested upgrades will allow this instrument to accomplish much more. The addition of the requested instrumentation will leverage significantly enhanced biomedical research capabilities for a broad group of researchers on the MSU-Bozeman campus. The requested instrumentation will also provide opportunities for new research directions in translational biomedical research, will support expanded systems biology approaches at MSU, and will contribute to the training and employment of numerous graduate students, post-doctoral fellows, and research staff. PUBLIC HEALTH RELEVANCE: We request support from the NIH to enhance the nuclear magnetic resonance (NMR) biomedical research capabilities of Montana State University. The requested instrumentation will enhance the research capabilities of a broad group of scientists involved in better understanding the molecular basis of iron homeostasis, host-pathogen interactions, viral infections, Alzheimer's, diabetes, AIDS, and other important human diseases.